Prethymic T-cell development defined by the expression of paired immunoglobulin-like receptors

Masuda, Kyoko; Kubagawa, Hiromi; Ikawa, Tomokatsu; Chen, Ching-Cheng; Kakugawa, Kiyokazu; Hattori, Masao; Kageyama, Ryoichiro; Cooper, Max D.; Minato, Nagahiro; Katsura, Yoshiteru; Kawamoto, Hiroshi

doi:10.1038/sj.emboj.7600878

Cited by 70 publications

(70 citation statements)

References 56 publications

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“…Murine stromal cell line TSt-4 cells were retrovirally transduced with the murine DLL-1 gene (TSt-4/DLL-1) (12). Cells of FT subpopulations (200 or 500 cells/well) were cultured in a well of 24-well plate monolaid with TSt-4/DLL1.…”

Section: Coculture With Stromal Cellsmentioning

confidence: 99%

T Cell Lineage Determination Precedes the Initiation of TCRβ Gene Rearrangement

Masuda

Kakugawa

Nakayama

et al. 2007

The Journal of Immunology

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Loss of dendritic cell potential is one of the major events in intrathymic T cell development, during which the progenitors become determined to the T cell lineage. However, it remains unclear whether this event occurs in synchrony with another important event, TCRβ chain gene rearrangement, which has been considered the definitive sign of irreversible T cell lineage commitment. To address this issue, we used transgenic mice in which GFP expression is controlled by the lck proximal promoter. We found that the double-negative (DN) 2 stage can be subdivided into GFP− and GFP+ populations, representing functionally different developmental stages in that the GFP−DN2, but not GFP+DN2, cells retain dendritic cell potential. The GFP+DN2 cells were found to undergo several rounds of proliferation before the initiation of TCRβ rearrangement as evidenced by the diversity of D-Jβ rearrangements seen in T cells derived from a single GFP+DN2 progenitor. These results indicated that the determination step of progenitors to the T cell lineage is a separable event from TCRβ rearrangement.

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Section: Coculture With Stromal Cellsmentioning

confidence: 99%

T Cell Lineage Determination Precedes the Initiation of TCRβ Gene Rearrangement

Masuda

Kakugawa

Nakayama

et al. 2007

The Journal of Immunology

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“…To address which step of DN stages is affected by Mint deficiency, we used the in vitro T cell differentiation assay that was originally developed by Schmitt and Zuniga-Pflucker (41). Lin Ϫ ScaI hi c-Kit hi (LSK) cells were sorted from E14.5 fetal livers, and their T cell differentiation was recapitulated on Tst-4/Dll1, a thymic stromal cell line Tst-4 expressing Dll1 (42,43). Differentiation of cultured cells was analyzed for their expression of Thy1.2 and CD19.…”

Section: Defective Dp T Cell Development In the Absence Of Mintmentioning

confidence: 99%

“…LSK cells were sorted from E14.5 fetal livers of mint Ϫ/Ϫ or mint ϩ/Ϫ embryos, seeded on a monolayer of Tst-4/Dll1, a thymus-derived stromal cell line expressing Dll1, or a parental cell line Tst-4 (42,43). Six to 14 days after in vitro culture, cells generated from LSK cells were harvested and subjected to FACS analysis.…”

mentioning

confidence: 99%

Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling

Tsuji¹,

Shinkura²,

Kuroda³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…15 Paired immunoglobulin-like receptor-expressing lin Ϫ c-kit ϩ IL-7R␣ ϩ cells in E11 fetal liver have been shown to be the precursor of T, NK, and dendritic cells and candidate prethymic T-cell progenitor cells. 16 T-committed progenitors have also been detected in E15.5 fetal blood. 17 These results suggest that T lymphoidcommitted progenitors (but not multipotent progenitors or HSCs) colonize the fetal thymus at E11.…”

Section: Introductionmentioning

confidence: 97%

Autonomous murine T-cell progenitor production in the extra-embryonic yolk sac before HSC emergence

Yoshimoto¹,

Porayette²,

Glosson³

et al. 2012

Blood

152

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The extra-embryonic yolk sac (YS) is the first hematopoietic site in the mouse embryo and is thought to generate only primitive erythroid and myeloerythroid progenitor cells before definitive HSC emergence within the embryo on E10.5. Here, we have shown the existence of T cell-restricted progenitors in the E9.5 YS that directly engraft in recipient immunodeficient mice. T-cell progenitors were also produced in vitro from both YS and para-aortic splanchnopleura hemogenic endothelial cells, and these T-cell progenitors repopulated the thymus and differentiated into mature T-cell subsets in vivo on transplantation. Our data confirm that the YS produces T-lineage-restricted progenitors that are available to colonize the thymus and provide new insight into the YS as a definitive hematopoietic site in the mouse embryo. (Blood. 2012;119(24): 5706-5714) IntroductionEmbryonic stem (ES) or induced pluripotent stem (iPS) cells have been intensively studied to understand the mechanisms regulating stem cell self-renewal and cell lineage specification and differentiation. Because ES-cell differentiation into the hematopoietic lineage mirrors the earliest aspects of normal embryonic development, 1 it is important to understand the process of developmental hematopoiesis to anticipate the products of ES or iPS differentiation. The first blood progenitor cells appear in the extra-embryonic yolk sac (YS) on E7.0. 2 These nucleated red blood cells express embryonic hemoglobin molecules and are called primitive erythroid progenitors. On E8.25, erythroid progenitor cells that express adult-type hemoglobin molecules appear in the YS and are called definitive erythroid progenitors. Likewise, primitive and definitive myeloid cells and megakaryocytes emerge in distinct waves in the YS. 3,4 HSCs, which reconstitute all the blood cell lineages that arise in adult mouse BM emerge at E10.5 in the ventral endothelial lining of the aorta in the aorta-gonad-mesonephros (AGM) region, 5,6 followed soon after on E11 in the YS, fetal liver, and placenta. 7,8 Later in development, HSCs accumulate in the fetal liver before mobilization and emigration into the BM just before birth. In adult mice, medullary HSCs self-renew and provide homeostatic blood cell production throughout life.T lymphocytes are produced and matured in the thymus, but, because there are no self-renewing stem cells in the thymus, T lymphopoiesis depends on circulating progenitor cells to continuously replenish the organ with precursors. Which BM hematopoietic progenitors colonize the adult thymus has long been controversial, but recent reports suggest that early T-lineage progenitors (lin Ϫ CD44 ϩ CD25 Ϫ CD117 ϩ IL-7R␣ loϪneg ) are the most immature T-cell progenitors found in the murine thymus. 9 Fetal T lymphopoiesis is also initiated by the colonization of extrathymic progenitor cells into the thymic anlage at E11. 10 The site and tissue of T-lymphoid progenitor emergence remains obscure. Interestingly, T, B, and myeloid lineage-committed progenitor cells, as well as multipoten...

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Prethymic T-cell development defined by the expression of paired immunoglobulin-like receptors

Cited by 70 publications

References 56 publications

T Cell Lineage Determination Precedes the Initiation of TCRβ Gene Rearrangement

T Cell Lineage Determination Precedes the Initiation of TCRβ Gene Rearrangement

Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling

Autonomous murine T-cell progenitor production in the extra-embryonic yolk sac before HSC emergence

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